Thyroid - Pathoma

Thyroglossal Duct Cysts
  • Thyroid develops at base of duct
  • Travels up thyroglossal duct to anterior neck
  • Duct should involute
  • So this is cystic dilation of duct remnant
  • Presents
    • Anterior neck mass
    • Mostly 15-30 yo
Lingual Thyroid
  • Persistent thyroid tissue at base of tongue
  • Mass at base of tongue
HYPERTHYROIDISM
  • Too much thyroid hormoe (TH)
  • Presents
    • Inc BMR
      • Due to inc synthesis of Na+ K+ ATPase
      • Weight loss despite inc appetite
      • Heat intolerance
      • Sweating
  • Inc sympathetic nervous activity
    • Due to increased β1 adrenergic R expression
    • Tachycardia
    • Inc Cardiac Output
    • Arrhythmias
      • especially A-Fib
      • esp in elderly
    • Tremor
    • Anxiety
    • Insomnia
    • Emotional
    • Staring gaze with lid lag
    • Diarrhoea with malabsorption
    • Oligomenorrhea
  • Bone resorption - leading to hypercalcaemia
  • Dec muscle mass, weakness
  • Hypocholesterolaemia - inc LDL Rs on cells
  • Hyperglycaemia
    • Gluconeogenesis
    • Glycogenolysis
  • Jod-Basedow phenomenon
    • Temporary hyperthyroidism due to the ingestion of small amount of iodine containing substance
    • Only happens if abnormal thyroid
  • Wolff–Chaikoff effect
    • Basically opposite of above
    • Temp hypothyroidism after the ingestion of large amount of iodine
    • Bigger effect seen in Graves' pts
Graves Disease
  • IgG vs TSH R
  • Inc synthesis, release of TH
  • Most common form of hyperthyroidism
  • Mostly women of child bearing age
  • Presents
      • Hyperthyroidism
      • Diffuse goiter
        • TSH R stim causes hyperplasia
      • Exopthalmos
        • Fibroblasts behind eyes have TSH Rs too!
        • Over stimmed so secrete xs glycosaminoglycans
        • This causes swelling due to this stuff getting stuck behind eye
      • Pretibial myxoedema
        • Same--fibroblast stim
        • (myx- means not watery-oedema but a myxoid substance, this case glycosaminoglycans)
        • feels "doughy"
      • Hyperplasia of thyroid follicles
      • Scalloping of colloid - get white spaces between colloid and epithelium of follicle
        Shown at high power, the tall columnar thyroid epithelium with Graves disease lines the hyperplastic infoldings into the colloid. Note theclear vacuoles in the colloid next to the epithelium where the increased activity of the epithelium to produce increased thyroid hormone has led to scalloping out of the colloid in the follicle.
        http://library.med.utah.edu/WebPath/ENDOHTML/ENDO023.html
  • Labs
    • Inc total and free T4
    • Dec TSH 
      • free T4 -ve feedback to anterior pituitary
      • T4 causes downregulation of TRH Rs in ant pit so can't respond to TRH
    • Hypocholesterolaemia
    • Hyperglycaemia
  • Rx
    • β blockers
    • Thioamide
      • Blocks peroxidase
      • This catalyses oxidation, organification and coupling steps
    • Propylthiouracil - PTU
      • Dec TH synth - inhibits organification of iodine as blocks gland oxidising it
      • Dec T4 to T3 conversion - blocks type I deiodinase  so block peripheral conversion
    • Radioiodine ablation
  • Complication: Thyroid storm
    • Triggered by massive hormone excess, elevated catecholamines
      • e.g. due to stress - eg childbirth
    • Arrhythmia
    • Hyperthermia
    • Vomiting
    • Hypovolaemic shock
    • Rx
      • Propylthiouracil 
      • β blockers
      • Steroids
  • Multinodular Goiter
    • Enlarged thyroid with multiple nodules
    • Cause: relative thyroid deficiency
    • Usually non-toxic - so remain euthyroid
    • Rare: parts become TSH-independent = toxic goitre
HYPOTHYROIDISM

Cretinism
  • Hypothyroid in neonates and infants
  • Presents
    • Mental retardation
    • Short statute + skeletal abnormalities
    • Coarse facial features
    • Enlarged tongue
    • Umbilical hernia
  • Causes
    • Maternal hypothyroidism in early pregnancy
    • Thyroid agenesis
    • Dyshormonogenetic goiter
      • Can't make TH
      • Most common deficient enzyme: peroxidase
    • Iodine deficiency
Myxoedema
  • Child or adult hypothyroidism
  • Presents
    • Myoedema
      • Dough like non-water oedema
      • Glycosaminoglycans in tissues and skin
      • Especially in larynx so deepening of voice and enlarged tongue
    • Weight gain with normal appetite = dec sympathetic activity and BMR
    • Slowed cognition
    • Muscle weakness
    • Cold intolerance
    • Dec sweating
    • Bradycardia
    • Dec cardiac output - fatigue, breathlessness
    • Oligomenorrhoea
    • Hypercholesterolaemia
    • Constipation
  • Causes
    • Hashimoto's thyroiditis
      • Most common in West
      • Autoimmune destruction of thyroid gland
    • Iodine deficiency
    • Drugs
      • Lithium
    • Surgical removal/radioablation

THYROIDITIS

Hashimoto's thyroiditis
  • Autoimmune desctruction of thyroid gland
  • Assoc: HLA-DR5
  • Most common cause of hypothyroid when sufficient iodine
  • Presents
    • Initial: hyperthyroidism
      • Destroy follicles
      • TH stored in these leak into blood
    • Then: hypothyroidism
      • Stored TH run out
      • Can't make more
    • Decreased T4
    • Inc TSH (T4 feedback reduces TRH Rs on ant pit so dec T4 means TRH R inc, so ant pit stimmed more to make TSH)
    • Antithyroglobulin, antimicrosomal [thyroid peroxidase antibody, TPO] Abs often
      • Don't mediate disease but show that there has been damage by the other Abs
      • +ve TPO & mild raised TSH signals future thyroid failure
  • Histo
    • Chronic inflammation
    • Germinal centres form
    • Fibrodis remains in capsule
    • Hürthle cells
      • Enlarged epithelial cells
      • Lots of pink, granular cytoplasm - altered mitochondria
      • (also seen in d toxic and nontoxic nodular goiter and follicular thyroid cancer)
  • Increased B cell lymphoma risk
    • As develop germinal centres, make post germinal centre B cells
    • Will become marginal zone
    • So marginal cell lymphoma risk - may present as Hashimoto's pt with newly growing thyroid
Subacute de Quervain Granulomatous Thyroiditis
  • Granulomatous thyroiditis
  • Post-viral (which is the acute bit!)
  • Presents
    • Tender thyroid
    • Transient hyperthyroidism
  • Self-limiting - no progression to hypothyroidism
Reidel's Fibrosing Thyroiditis
  • Chronic inflammation + extensive fibrosis of thyroid
  • Presnets
    • Mostly young females
    • Hypothyroid
    • Hard as wood, non-tender thyroid gland
    • Fibrosis may extend - e.g. larynx - cf Hashimoto's is intracapsular
    • NB need to diff from e.g. anaplasic carcinoma of thyroid (older people)
Subacute lymphocytic thyroiditis
  • Silent
  • Painless
  • Abs
  • Infiltrate
  • Some postpartum

AMIODERONE
  • Amioderone can cause both a hyper (thyrotoxicosis) or hypothyroid state
  • Cause
    • inhibits type 1 5'-deiodinase 
      • dec peripheral T4 to T3
      • dec clearance of T4 and rT3 (reverse T3)
      • T4 and rT3 serum levels drop by 20-25%
    • inhibits T4 and T3 entry into tissues
      • this incs serum levels - 40%
    • inhibits 2,5'-deiodinase in pituitary
      • thus inc TSH secretion
      • may have dec response to TRH
    • direct toxicity to thyroid follicular cells
    • competitive antagonist for T3 in cardiac cells
  • Hypo' cases may be due to inc progression of Hashimoto's thyroiditis

EUTHYROID SICK SYNDROME
  • Get inc levels of rT3 (reverse T3 - a T3 isomer)
  • Low T4
  • Low T3
  • Yet thyroid appears normal
  • Causes
    • pneumonia
    • fasting, starvation, anorexia nervosa
    • sepsis
    • trauma
    • cardiopulmonary bypass
    • malignancy
    • stress
    • heart failure
    • hypothermia
    • MI
    • CKD
    • cirrhosis
    • diabetic ketoacidosis

THYROID NEOPLASIAhttps://wiki.uiowa.edu/display/protocols/Head+and+Neck+Pathology 
  • thyroglobulin used as a tumour marker
  • Distinct, solitary nodule
  • MOST nodules benign
  • 131-Iodine uptake studies
    • Inc in Graves, nodular goitre
    • Dec in  adenoma, carcinoma
      • Do fine needle aspiration biopsy - no bigger as v vascular
    • "hot" nodules have increased take up
    • "cold" uptake less than the rest of the normal thyroid
Follicular Adenoma
  • Benign prolif of follicules surrounded by fibrous capsule
  • Most non functional
Carcinoma: 4 Types
  1. Papillary Carcinoma
    • Most common thyroid carcinoma - 80%
    • Exposure to ionising radiation in childhood = major risk factor
      • e.g. if irradiated for severe acne back in the day
    • Orphan Annie Eye Nuclei - uniform staining and light so look "clear"
    • Nuclear grooves - lines within nuclei
    • Calcification leading to psamomma body - layers of calcification
    • Overlapping nuclei
    • Spread: to cervical lymph nodes
    • Excellent prognosis
  2. Follicular Carcinoma
    • Malignant proliferation of follicles
    • Surrounded by fibrous capsule but invade through capsule
    • Note that fine needle aspiration biopsy can't distinguish this from benign follicular adenoma as the only difference microscopically is the invasion of the capsule
    • Haematogenous spread
  3. Medullary Carcinoma
    • Malifnant prolif of parafollicular C cells
    • Present
      • High calcitonin - made by tumour
      • May cause hypocalcaemia
      • Some of the calcitonin may be deposited locally in tumour as local amyloidosis
      • "Malignant cells in amyloid stroma"
    • Familial
      • MEN2A and MEN2B
        • MEN2A - late adolescent
          • Medullary carcinoma of thyroid
          • Phaeochromocytoma
          • Parathyroid adenomas
        • MEN2B - young child
          • Medullary carcinoma of thyroid
          • Phaeochromocytoma
          • Ganglioneuromas - esp of oral mucosa
    • Assoc with RET oncogene muts
    • If RET mut, warrants prophylactic thyroidectomy!
  4. Anaplastic Carcinoma
    • Undiff highly malignant tumour
    • Mostly old people
    • Often invades local structures
      • Dysphagia
      • Respiration compromise
      • (cf Reidel's fibrosing thyroiditis - seen in young)
    • Poor prognosis
    • Biopsy - highly malignant, undiff (ie anaplastic--no normal structures)


Robbins Basic Pathology, Robbins Pathologic Basis of Disease, Robbins Review of Pathology (MCQs - very path-y), Robbins Flash Cards, Baby Robbins, Robbins Atlas - some exact same images come up in the exam, 100 Cases in ClinicalPathology - possibly the best Qbank for the practical